There is increasing evidence suggesting underlying abnormalities in sarcolemmal function of vascular smooth muscle in hypertension. Evidence from several laboratories, including ours, indicates that the activity of the membrane sodium pump may be decreased, especially in volume-expanded forms of hypertension. A humoral inhibitor substance has been suggested. Such pump inhibition may account for several manifestations of hypertension, including increased arterial resistance, decreased venous compliance, increased cardiac performance, and non-pressure-related "waterlogging" and hypertrophy of vascular walls. In this proposed project we will continue our studies of sodium pump function and presumably related phenomena in hypertension. We will measure ouabain-sensitive Rb86 uptake, (H3)-ouabain binding, (V-P32)-ATPase binding, Na ion, K ion-ATPase activity and membrane potentials of vascular smooth muscle cells, body fluid volumes, and vascular wall composition in several forms of experimental and clinical hypertension. We will attempt to answer the following questions: 1) Is decreased pump activity associated in time and magnitude with the increased vascular resistance and arterial pressure in hypertension? 2) In which forms of experimental and clinical hypertension may decreased pump activity play a role? 3) Does decreased pump function account for changes in vascular composition in hypertension? 4) Is decreased pump activity in hypertension the result of a decreased number of pump molecules or a decreased activity of a normal number of pump molecules? 5) Is there a humoral factor that decreases pump activity in hypertension? The long term goal of this program is to describe the state of the sodium pump in cardiovascular muscle in hypertension and use that information to develop new approaches to antihypertensive therapy.